Sakamoto, K. M. et al. PROTACs: chimeric molecules that target proteins to the Skp1–Cullin-F box complex for ubiquitination and degradation. Proc. Natl Acad. Sci. USA 98, 8554–8559 (2001).
Banik, S. M. et al. Lysosome-targeting chimaeras for degradation of extracellular proteins. Nature 584, 291–297 (2020).
Pance, K. et al. Modular cytokine receptor-targeting chimeras for targeted degradation of cell surface and extracellular proteins. Nat. Biotechnol. 41, 273–281 (2023).
Alabi, S. B. & Crews, C. M. Major advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs. J. Biol. Chem. 296, 100647 (2021).
Bekes, M., Langley, D. R. & Crews, C. M. PROTAC targeted protein degraders: the past is prologue. Nat. Rev. Drug Discov. 21, 181–200 (2022).
Chen, Y. et al. Small-molecule ferritin degrader as a pyroptosis inducer. J. Am. Chem. Soc. 145, 9815–9824 (2023).
Wei, J. et al. Harnessing the E3 ligase KEAP1 for targeted protein degradation. J. Am. Chem. Soc. 143, 15073–15083 (2021).
Imaide, S. et al. Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity. Nat. Chem. Biol. 17, 1157–1167 (2021).
Caianiello, D. F. et al. Bifunctional small molecules that mediate the degradation of extracellular proteins. Nat. Chem. Biol. 17, 947–953 (2021).
Ahn, G. et al. LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation. Nat. Chem. Biol. 17, 937–946 (2021).
Guedeney, N., Cornu, M., Schwalen, F., Kieffer, C. & Voisin-Chiret, A. S. PROTAC technology: a new drug design for chemical biology with many challenges in drug discovery. Drug Discov. Today 28, 103395 (2023).
Chen, Y. et al. Proteolysis-targeting chimera (PROTAC) delivery system: advancing protein degraders towards clinical translation. Chem. Soc. Rev. 51, 5330–5350 (2022).
Garber, K. The PROTAC gold rush. Nat. Biotechnol. 40, 12–16 (2022).
Ahn, G. et al. Elucidating the cellular determinants of targeted membrane protein degradation by lysosome-targeting chimeras. Science 382, eadf6249 (2023).
Gadd, M. S. et al. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nat. Chem. Biol. 13, 514–521 (2017).
Takahashi, D. et al. AUTACs: cargo-specific degraders using selective autophagy. Mol. Cell 76, 797–810.e10 (2019).
Li, Z. et al. Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds. Nature 575, 203–209 (2019).
Stanton, B. Z., Chory, E. J. & Crabtree, G. R. Chemically induced proximity in biology and medicine. Science 359, eaao5902 (2018).
Bai, L. et al. A potent and selective small-molecule degrader of STAT3 achieves complete tumor regression in vivo. Cancer Cell 36, 498–511.e17 (2019).
Chirnomas, D., Hornberger, K. R. & Crews, C. M. Protein degraders enter the clinic—a new approach to cancer therapy. Nat. Rev. Clin. Oncol. 20, 265–278 (2023).
Wurz, R. P. et al. Affinity and cooperativity modulate ternary complex formation to drive targeted protein degradation. Nat. Commun. 14, 4177 (2023).
Tamura, T. et al. Rapid labelling and covalent inhibition of intracellular native proteins using ligand-directed N-acyl-N-alkyl sulfonamide. Nat. Commun. 9, 1870 (2018).
Beerkens, B. L. H. et al. N-Acyl-N-alkyl sulfonamide probes for ligand-directed covalent labeling of GPCRs: the adenosine A2B receptor as case study. ACS Chem. Biol. 19, 1554–1562 (2024).
Kawano, M. et al. Lysine-reactive N-acyl-N-aryl sulfonamide warheads: improved reaction properties and application in the covalent inhibition of an ibrutinib-resistant BTK mutant. J. Am. Chem. Soc. 145, 26202–26212 (2023).
Caldas-Lopes, E. et al. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc. Natl Acad. Sci. USA 106, 8368–8373 (2009).
Schopf, F. H., Biebl, M. M. & Buchner, J. The HSP90 chaperone machinery. Nat. Rev. Mol. Cell Biol. 18, 345–360 (2017).
Cuesta, A., Wan, X., Burlingame, A. L. & Taunton, J. Ligand conformational bias drives enantioselective modification of a surface-exposed lysine on HSP90. J. Am. Chem. Soc. 142, 3392–3400 (2020).
Filippakopoulos, P. et al. Selective inhibition of BET bromodomains. Nature 468, 1067–1073 (2010).
Zhou, X. et al. Therapeutic targeting of BET bromodomain protein, BRD4, delays cyst growth in ADPKD. Hum. Mol. Genet. 24, 3982–3993 (2015).
Bondeson, D. P. et al. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat. Chem. Biol. 11, 611–617 (2015).
Wang, C. et al. In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy. Nat. Biomed. Eng. 1, 0011 (2017).
Hu, Q. et al. Inhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets. Nat. Biomed. Eng. 5, 1038–1047 (2021).
Wang, Y. et al. Active recruitment of anti-PD-1-conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy. Sci. Adv. 9, eadf6854 (2023).
Michael, J. V. et al. Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress tumor growth. Blood 130, 567–580 (2017).
Zengerle, M., Chan, K. H. & Ciulli, A. Selective small molecule induced degradation of the BET bromodomain protein BRD4. ACS Chem. Biol. 10, 1770–1777 (2015).
Hu, J. et al. Precise conformational control yielding highly potent and exceptionally selective BRD4 degraders with strong antitumor activity. J. Med. Chem. 66, 8222–8237 (2023).
Jia, H. et al. Immunotherapy for triple-negative breast cancer: existing challenges and exciting prospects. Drug Resist. Updat. 32, 1–15 (2017).
Gangi, A. et al. Breast-conserving therapy for triple-negative breast cancer. JAMA Surg. 149, 252–258 (2014).
Trepel, J., Mollapour, M., Giaccone, G. & Neckers, L. Targeting the dynamic HSP90 complex in cancer. Nat. Rev. Cancer 10, 537–549 (2010).
Wang, X. et al. The regulatory mechanism of HSP90α secretion and its function in tumor malignancy. Proc. Natl Acad. Sci. USA 106, 21288–21293 (2009).
Li, W. et al. Extracellular HSP90 (eHSP90) as the actual target in clinical trials: intentionally or unintentionally. Int. Rev. Cell Mol. Biol. 303, 203–235 (2013).
Murshid, A., Gong, J., Stevenson, M. A. & Calderwood, S. K. Heat shock proteins and cancer vaccines: developments in the past decade and chaperoning in the decade to come. Expert Rev. Vaccines 10, 1553–1568 (2011).
Hance, M. W. et al. Secreted HSP90 is a novel regulator of the epithelial to mesenchymal transition (EMT) in prostate cancer. J. Biol. Chem. 287, 37732–37744 (2012).
Cheng, C. F. et al. Transforming growth factor α (TGFα)-stimulated secretion of HSP90α: using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFβ-rich environment during wound healing. Mol. Cell. Biol. 28, 3344–3358 (2008).
Loppinet, E. et al. Targeted lysosomal degradation of secreted and cell surface proteins through the LRP-1 pathway. J. Am. Chem. Soc. 145, 18705–18710 (2023).
Prasad, J. M., Migliorini, M., Galisteo, R. & Strickland, D. K. Generation of a potent low density lipoprotein receptor-related protein 1 (LRP1) antagonist by engineering a stable form of the receptor-associated protein (RAP) D3 domain. J. Biol. Chem. 290, 17262–17268 (2015).
Secli, L., Fusella, F., Avalle, L. & Brancaccio, M. The dark-side of the outside: how extracellular heat shock proteins promote cancer. Cell. Mol. Life Sci. 78, 4069–4083 (2021).
Li, C. W. et al. Eradication of triple-negative breast cancer cells by targeting glycosylated PD-L1. Cancer Cell 33, 187–201.e10 (2018).
Patel, S. R., Hartwig, J. H. & Italiano, J. E. Jr. The biogenesis of platelets from megakaryocyte proplatelets. J. Clin. Invest. 115, 3348–3354 (2005).
Garcia, B. A. et al. The platelet microparticle proteome. J. Proteome Res. 4, 1516–1521 (2005).
Hu, C. M. et al. Nanoparticle biointerfacing by platelet membrane cloaking. Nature 526, 118–121 (2015).
Fang, R. H., Gao, W. & Zhang, L. Targeting drugs to tumours using cell membrane-coated nanoparticles. Nat. Rev. Clin. Oncol. 20, 33–48 (2023).
